JPH1072361A - Tnf-producing depressant from tea leaf extract - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine which suppresses the excess production of tumor necrosis factor(TNF) and is effective for improvement of inflammation and the like accompanied by an allergic reaction by using an extract of tea leaves as an active ingredient. SOLUTION: This medicine contains an extract of leaves if Camellia sinensis L., namely tea leaves, as an active ingredient. The extract is obtained by using green tea, oolong tea and red tea as a raw material and extracting it with water. an organic solvent and its mixed solvent. For example, 2.94g of the extract of tea leaves is obtained by adding 41 of purified water to 100g of green tea, extracting at 80 deg.C for 10min., concentrating one eight amount of the extracted solution under reduced pressure and then lyophilizing it. The extract of tea leaves thus obtained is orally admistreated as powders, granules and tablets by formulating a pharmaceutically permissible carrier there with and used as preparations for external use, e.g. ointments, and also utilized as a toilet lotion and the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a tea leaf extract TNF.
The present invention relates to an invention based on a production suppressing action. For more information,
The present invention relates to a TNF production inhibitor which suppresses overproduction of TNF and is effective in improving various inflammations based on overproduction of TNF, for example, bronchitis, bronchial asthma, pollinosis or skin inflammation including atopy.

[0002]

2. Description of the Related Art TNF (Tumor Necrosis Factor) not only has a direct inhibitory effect on cancer cells (growth inhibition, necrosis), but also a series of inflammations that occur when a living body is externally stimulated. It is a cytokine that is involved in the reaction from its development to progress, termination and repair. It also plays a role in bridging the inflammatory response to the immune response, and is also involved in cell differentiation and maturation. On the other hand, excessive production of TNF causes pathological inflammation. Contact hypersensitivity and atopic dermatitis
NF is produced locally and is thought to be involved in the exacerbation of the condition. In fact, the symptoms of contact hypersensitivity are alleviated if the action of TNF is suppressed by an anti-TNF antibody.

[0003] Japanese Patent Application Laid-Open No. Hei 7-215884 discloses a composition obtained by grinding the leaves of a Labiatae plant and extracting it with an organic solvent such as water or ethanol or a mixture thereof.
There is disclosed a perilla extract having a TNF production inhibitory effect, which is obtained by removing perylaldehyde and a fraction having a molecular weight of 10,000 or more. The publication also discloses that this perilla extract is effective for allergic diseases such as atopic dermatitis.

JP-A-3-157330 discloses that epigallocatechin gallate, a component of tea ( Camellia sinensis L. ) leaves, is effective as an antiallergic agent. However, it is not known that the tea leaf extract has a TNF production inhibitory action.

[0005]

An object of the present invention is to provide a TNF production inhibitor comprising a tea leaf extract as an active ingredient. Another object of the present invention is to provide a TNF production inhibitor that is effective not only in inflammation accompanied by an allergic reaction but also in inflammation that is less or not accompanied by an allergic reaction. Still another object of the present invention is, therefore, skin inflammation, including, for example, atopic dermatitis,
An object of the present invention is to provide a TNF production inhibitor which is effective in improving inflammatory diseases such as hay fever, bronchitis, bronchial asthma and the like, and is highly safe. Still other objects and advantages of the present invention will become apparent from the following description.

[0006]

According to the present invention, the above objects and advantages of the present invention are achieved, firstly, by a TNF production inhibitor characterized by comprising a tea leaf extract. As described above, the leaves of tea ( Camellia sinensis L. ), that is, extracts of tea leaves, can be used as such as the TNF production inhibitor in the present invention. The tea leaf extract is obtained by using green tea, oolong tea, and black tea as raw materials and performing an extraction treatment with water, an organic solvent, and a mixture thereof. It can be used as an extract or powdered by spray drying or freeze drying. Examples of the organic solvent used for the extraction include lower alcohols such as methanol and ethanol, acetone, and chloroform. Hot water is preferred as the extraction solvent.

[0007] The TNF production inhibitor or the composition for suppressing TNF production of the present invention comprises powders, granules, tablets, capsules by mixing a tea leaf extract as an active ingredient and a pharmaceutically acceptable carrier. Preparations, syrups, solutions, suspensions,
It can be in the form of an emulsion and can be administered orally. It can also be used as an external preparation such as an ointment, liniment and lotion. When used as cosmetics or quasi-drugs, lotions, emulsions, creams, shampoos, rinses,
Use for soaps, talcum powders, bath additives, wet tissues in which a non-woven cloth contains a lotion, and the like can be mentioned.
It can also be used by impregnating and adsorbing sanitary cotton and fibers. When used as a food material, it can be included in foods preferred by the recipient as foods that improve inflammatory diseases. Next, Production Examples and Examples of the present invention will be described.

[0008]

【Example】

[Production Example 1] Production of tea leaf extract 4 liters of purified water was added to 100 g of green tea, and 1
Extracted for 0 minutes. After concentrating 1/8 of the extract under reduced pressure,
Lyophilized to obtain 2.94 g of tea leaf extract (Sencha 12.5
g).

Example 1 Inhibition of TNF Production in Mice by Tea Leaves Extract Romultide (a derivative of muramyl peptide, manufactured by Daiichi Pharmaceutical Co., Ltd.), which is an immunostimulant, was administered to ICR mice in an amount of 0.5 mg. 20 mg of the produced green tea extract was orally administered simultaneously. After 3 hours, the stimulant OK-
432 (trade name: Picibanil, manufactured by Chugai Pharmaceutical Co., Ltd.) was injected intravenously at a dose of 3 KE / mouse, blood was collected 2 hours later, TNF in the blood was measured, and a control group to which no sencha extract was administered. Compared. The measurement of TNF was performed by a bioassay using L-929 cells (J. Biol. Res.
Modof., 5, 117-123 (1986)). Table 1 shows the results. The blood TNF level of untreated mice is usually 1 U / ml or less, but the blood TNF level of the control group mice to which romultide and OK-432 were administered was 214.5 U / ml.
Up. On the other hand, in the mice to which 20 mg of the sencha extract was administered, the TNF level was 51.5 U / ml, indicating that TNF production was suppressed.

[0010]

[Table 1]

Example 2 Inhibition of TNF Production by Tea Leaf Extract and Perilla Extract Teafuran 30A (E, a tea leaf extract manufactured by ITO EN Co., Ltd.)
GCg: 12-22%, containing caffeine 5-6%) 20
mg or Akadiso extract (Literature: Biosci. Biotech. Bi
ochem., 56, 152 (prepared by the method described in 1992)) 0.4 ml
(Containing 20 mg or more of solids) was orally administered, and the TNF production inhibitory effect was examined by the method described in Example 1. Table 2 shows the results. TNF blood level of the control mice was 27
9.3 U / ml, whereas theafran 30
In the mice receiving A or Akadiso extract, blood levels were reduced to 13.1 U / ml and 16.6 U / ml, respectively.

[0012]

[Table 2]

[Example 3] Inhibitory effect of tea leaf extract on TNF production in vitro Mouse peritoneal macrophages induced by glycogen were collected and lipopolysaccharide (LPS) (1.0 ng /
ml) and the green tea extract prepared in Production Example 1 (6.25-8
(00 μg / ml), and after culturing for 2 hours, TNF in the supernatant was analyzed. Table 3 shows the results. In an untreated macrophage without addition of LPS, TN in the culture supernatant was
F was trace (0.0122 U / ml), but LPS
Treated, the concentration increased to 50 times or more (0.591 U / ml). On the other hand, the sencha extract suppressed in a concentration-dependent manner.

[0014]

[Table 3]

Example 4 Anti-inflammatory Effect of Green Tea Extract on Auricular Dermatitis of Mice Theoral administration of theafran 30A, a tea leaf extract manufactured by ITO EN Co., Ltd., to ICR mice twice at an interval of 18 hours, the second time Three hours after the administration, TPA (0.2 μg) or arachidonic acid (0.25 mg) was applied to the right ear to induce inflammation. After 4 hours, the weight of the pinna was measured to determine the degree of edema. Table 4 shows the results. TPA-induced pinna edema is a model of inflammation involving leukotrienes, and arachidonic acid-induced pinna edema is referred to as a model of prostaglandin-related inflammation. Theafuran 30A suppressed any edema in a dose-dependent manner and showed an anti-inflammatory effect.

[0016]

[Table 4]

[0017]

Industrial Applicability The TNF production inhibitor of the present invention and TNF
The composition for suppressing production remarkably suppresses TNF production by oral administration, and is useful for improving various inflammations.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Yuko Sakasaka 21 Goddess of Sagara-cho, Haibara-gun, Shizuoka Pref.

Claims (3)

[Claims] 1. A method for preparing a T extract, comprising a tea leaf extract.
NF production inhibitor. 2. A composition for suppressing TNF production, comprising a tea leaf extract. 3. Use of a tea leaf extract as a TNF production inhibitor.